The Journal of Neuroscience, November 1, 2000, 20(21):8051-8060
Activity-Dependent Patterning of Retinogeniculate Axons Proceeds
with a Constant Contribution from AMPA and NMDA Receptors
Carsten D.
Hohnke,
Serkan
Oray, and
Mriganka
Sur
Department of Brain and Cognitive Sciences, Massachusetts Institute
of Technology, Cambridge, Massachusetts 02139
Neural activity is critical for the refinement of neural circuitry
during development, although the mechanisms involved in stabilizing
appropriate connectivity remain unclear. It has been proposed that the
insertion of AMPA receptors at synapses with only NMDA receptors
("silent synapses") mediates this stabilization, leading to an
increasing contribution from AMPA receptors as development proceeds.
Here we show in a mammalian system known to undergo activity-dependent
development [the segregation of retinal afferents into ON/OFF
sublaminae in the ferret lateral geniculate nucleus (LGN)] that the
refinement of the neural circuitry occurs in the presence of a constant
functional contribution from AMPA and NMDA receptors. Although we
detected a small number of silent synapses on LGN cells, their
proportion did not decrease with age. The size and kinetics of
NMDA-mediated spontaneous EPSCs (sEPSCs) were also stable over this
period. Together with previous results reporting the stability of
unitary AMPA-mediated EPSCs, the constancy of NMDA-mediated sEPSCs
indicates an unchanging AMPA/NMDA contribution. Additionally, the
CNQX-sensitivity did not increase for either sEPSCs or optic
tract-evoked EPSCs. Likewise, the anatomical AMPA/NMDA ratio, as
assayed by quantifying the colocalized expression of AMPA and NMDA
receptor subunits, was fixed throughout ON/OFF sublamination. In
particular, the colocalization of AMPA receptor subunits (GluR1 or
GluR4) and NMDA receptor subunit NR1 opposite identified
retinogeniculate terminals was stable during this period. These results
add to the view of the population of retinogeniculate synapses as
robustly stable or normalized during a period when retinogeniculate
axons are undergoing dramatic activity-dependent refinement.
Key words:
visual system development; silent synapses; electrical
activity; NMDA receptors; AMPA receptors; lateral geniculate
nucleus
Copyright © 2000 Society for Neuroscience 0270-6474/00/20218051-10$05.00/0
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